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Desipramine and 2-Hydroxydesipramine Plasma Levels in Endogenous Depressed Patients: Lack of Correlation With Therapeutic Response

Desipramine and 2-Hydroxydesipramine Plasma Levels in Endogenous Depressed Patients: Lack of... Abstract • Studies of the relationship between plasma concentrations of desipramine hydrochloride and clinical response have shown contradictory results, and only one prior study examined 2-hydroxydesipramine and its relationship to treatment. We therefore performed a study in a large, carefully diagnosed group of depressed patients taking fixed maintenance doses of desipramine to elucidate a potential relationship between clinical response and plasma concentrations of desipramine and 2-hydroxydesipramine. There was no significant correlation between clinical response and steadystate plasma levels of desipramine, 2-hydroxydesipramine, or the sum of desipramine plus 2-hydroxydesipramine. Although some commercial laboratories suggest a specific therapeutic plasma level "range" for desipramine, our data provide no support for such a range, nor for the routine measurement of plasma desipramine and 2-hydroxydesipramine concentrations in depressed patients. References 1. Glassman AH, Perel JM, Shostak M, Kantor S, Fleiss J: Clinical implications of imipramine plasma levels for depressive illness . Arch Gen Psychiatry 1977;34:197-204.Crossref 2. Reisby, Gram LF, Beck P, Nagy A, Petersen GO, Ortman J, Ibsen I, Dencker SJ, Jacobsen 0, Krautwald O, Søndergaard I, Christiansen J: Imipramine: Clinical effects and pharmacokinetic variability . Psychopharmacology 1977;54:263-272.Crossref 3. Coppen A, Montgomery S, Ghose K, Rama Rao VA, Bailey J, Christiansen J, Mikkleson PL, van Praag HM, van der Poel F, Minsken EJ, Kozulja VG, Matussek N, Kungkunz G, Jorgensen A: Amitriptyline plasma concentration and clinical effect: A World Health Organization collaborative study . Lancet 1978;1:63-66.Crossref 4. Rickels K, Weise C, Case G, Hucker H: Tricyclic plasma levels in depressed outpatients treated with amitriptyline . Psychopharmacology 1983;80:14-18.Crossref 5. Asberg M, Cronholm B, Sjoqvist F, Tuck D: Relationship between plasma levels and therapeutic effect of nortriptyline . Br Med J 1971;3:331-334.Crossref 6. Montgomery S, Braithwaite R, Dawling S, McAuley R: High plasma nortriptyline levels in the treatment of depression . Clin Pharmacol Ther 1978;23:309-314. 7. Whyte SF, MacDonald AJ, Naylor GJ, Moody JP: Plasma concentrations of protriptyline and clinical effects in depressive women . Br J Psychiatry 1976;128:384-390.Crossref 8. Khalid R, Amin MM, Ban TA: Desipramine plasma levels and therapeutic response . Psychopharmacol Bull 1978;14:43-44. 9. Friedel RO, Veith RC, Bloom V, Bielski RJ: Desipramine plasma levels and clinical response in depressed outpatients . Community Psychopharmacol 1979;3:81-87. 10. Hrdina PD, Lapierre YD: Clinical response, plasma levels and pharmacokinetics of desipramine in depressed inpatients . Can Prog Neuropsychopharmacol 1980;4:591-600.Crossref 11. Stewart JW, Quitkin F, Fyer A, Rifkin A, McGrath P, Liebowitz M, Rosnick L, Klein DF: Efficacy of desipramine in endogenomorphically depressed patients . J Affective Disord 1980;2:165-176.Crossref 12. Brunswick DJ, Amsterdam JD, Potter L, Caroff S, Rickels K: Relationship between tricyclic antidepressant plasma levels and clinical response in patients treated with desipramine or doxepine . Acta Psychiatr Scand 1983;67:371-377.Crossref 13. Simpson GM, Pi EH, Abdelmalek E, Boyd JL, Carroll RS, Cooper TB, Miller A: Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients . Psychopharmacology 1983; 80:240-242.Crossref 14. Aberg-Wistedt A, Jostell KG, Ross SB, Westerlund D: Effects of zimelidine and desipramine on serotonin and noradrenaline uptake mechanisms in relation to plasma concentrations and to therapeutic effects during treatment of depression . Psychopharmacology 1981;74:297-304.Crossref 15. Nelson JC, Jatlow P, Quinlan DM, Bowers MB: Desipramine plasma concentration and antidepressant response . Arch Gen Psychiatry 1982;39:1419-1422.Crossref 16. Nelson JC, Block JL, Jatlow PI: Clinical implications of 2-hydroxy-desipramine plasma concentrations . Clin Pharmacol Ther 1983;33:183-189.Crossref 17. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria . Arch Gen Psychiatry 1978;35:773-782.Crossref 18. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;23:56-62.Crossref 19. Asberg M, Cronholm B, Sjoqvist F, Tuck D: Correlation of subjective side effects with plasma concentrations of nortriptyline . Br Med J 1970;4:18-21.Crossref 20. Amsterdam JD, Brunswick D, Potter L, Kaplan MJ: Cimetidineinduced alterations in desipramine plasma levels . Psychopharmacology 1984;83:373-375.Crossref 21. Suckow RF, Cooper TB: Simultaneous determination of imipramine, desipramine, and their 2-hydroxy metabolites in plasma by ion-pair reversed-phase high-performance liquid chromatography with amperometric detection . J Pharm Sci 1981;70:257-261.Crossref 22. ZarJH: Biostatistical Analysis . Englewood Cliffs, NJ, Prentice-Hall Inc, 1974. 23. Gram LF: Metabolism of tricyclic antidepressants: A review . Dan Med Bull 11974;21:218-231. 24. Potter WZ, Calil HM, Sutfin TA, Zavadil AP, Jusko WJ, Rapoport J, Goodwin FK: Active metabolites of imipramine and desipramine in man . Clin Pharmacol Ther 1982;32:393-401.Crossref 25. Narasimhachari N, Saady JJ, Joseph A, Ettigi P, Friedel RO: Evidence for in vivo methylation of the secondary amine antidepressant desipramine to imipramine . J Clin Psychopharmacol 1982;6:413-416. 26. Brunswick DJ, Mendels J: Reduced levels of tricyclic antidepressants in plasma from Vacutainers . Community Psychopharmacol 1977;1:131-134. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Desipramine and 2-Hydroxydesipramine Plasma Levels in Endogenous Depressed Patients: Lack of Correlation With Therapeutic Response

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References (28)

Publisher
American Medical Association
Copyright
Copyright © 1985 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1985.01790270051005
Publisher site
See Article on Publisher Site

Abstract

Abstract • Studies of the relationship between plasma concentrations of desipramine hydrochloride and clinical response have shown contradictory results, and only one prior study examined 2-hydroxydesipramine and its relationship to treatment. We therefore performed a study in a large, carefully diagnosed group of depressed patients taking fixed maintenance doses of desipramine to elucidate a potential relationship between clinical response and plasma concentrations of desipramine and 2-hydroxydesipramine. There was no significant correlation between clinical response and steadystate plasma levels of desipramine, 2-hydroxydesipramine, or the sum of desipramine plus 2-hydroxydesipramine. Although some commercial laboratories suggest a specific therapeutic plasma level "range" for desipramine, our data provide no support for such a range, nor for the routine measurement of plasma desipramine and 2-hydroxydesipramine concentrations in depressed patients. References 1. Glassman AH, Perel JM, Shostak M, Kantor S, Fleiss J: Clinical implications of imipramine plasma levels for depressive illness . Arch Gen Psychiatry 1977;34:197-204.Crossref 2. Reisby, Gram LF, Beck P, Nagy A, Petersen GO, Ortman J, Ibsen I, Dencker SJ, Jacobsen 0, Krautwald O, Søndergaard I, Christiansen J: Imipramine: Clinical effects and pharmacokinetic variability . Psychopharmacology 1977;54:263-272.Crossref 3. Coppen A, Montgomery S, Ghose K, Rama Rao VA, Bailey J, Christiansen J, Mikkleson PL, van Praag HM, van der Poel F, Minsken EJ, Kozulja VG, Matussek N, Kungkunz G, Jorgensen A: Amitriptyline plasma concentration and clinical effect: A World Health Organization collaborative study . Lancet 1978;1:63-66.Crossref 4. Rickels K, Weise C, Case G, Hucker H: Tricyclic plasma levels in depressed outpatients treated with amitriptyline . Psychopharmacology 1983;80:14-18.Crossref 5. Asberg M, Cronholm B, Sjoqvist F, Tuck D: Relationship between plasma levels and therapeutic effect of nortriptyline . Br Med J 1971;3:331-334.Crossref 6. Montgomery S, Braithwaite R, Dawling S, McAuley R: High plasma nortriptyline levels in the treatment of depression . Clin Pharmacol Ther 1978;23:309-314. 7. Whyte SF, MacDonald AJ, Naylor GJ, Moody JP: Plasma concentrations of protriptyline and clinical effects in depressive women . Br J Psychiatry 1976;128:384-390.Crossref 8. Khalid R, Amin MM, Ban TA: Desipramine plasma levels and therapeutic response . Psychopharmacol Bull 1978;14:43-44. 9. Friedel RO, Veith RC, Bloom V, Bielski RJ: Desipramine plasma levels and clinical response in depressed outpatients . Community Psychopharmacol 1979;3:81-87. 10. Hrdina PD, Lapierre YD: Clinical response, plasma levels and pharmacokinetics of desipramine in depressed inpatients . Can Prog Neuropsychopharmacol 1980;4:591-600.Crossref 11. Stewart JW, Quitkin F, Fyer A, Rifkin A, McGrath P, Liebowitz M, Rosnick L, Klein DF: Efficacy of desipramine in endogenomorphically depressed patients . J Affective Disord 1980;2:165-176.Crossref 12. Brunswick DJ, Amsterdam JD, Potter L, Caroff S, Rickels K: Relationship between tricyclic antidepressant plasma levels and clinical response in patients treated with desipramine or doxepine . Acta Psychiatr Scand 1983;67:371-377.Crossref 13. Simpson GM, Pi EH, Abdelmalek E, Boyd JL, Carroll RS, Cooper TB, Miller A: Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients . Psychopharmacology 1983; 80:240-242.Crossref 14. Aberg-Wistedt A, Jostell KG, Ross SB, Westerlund D: Effects of zimelidine and desipramine on serotonin and noradrenaline uptake mechanisms in relation to plasma concentrations and to therapeutic effects during treatment of depression . Psychopharmacology 1981;74:297-304.Crossref 15. Nelson JC, Jatlow P, Quinlan DM, Bowers MB: Desipramine plasma concentration and antidepressant response . Arch Gen Psychiatry 1982;39:1419-1422.Crossref 16. Nelson JC, Block JL, Jatlow PI: Clinical implications of 2-hydroxy-desipramine plasma concentrations . Clin Pharmacol Ther 1983;33:183-189.Crossref 17. Spitzer RL, Endicott J, Robins E: Research diagnostic criteria . Arch Gen Psychiatry 1978;35:773-782.Crossref 18. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;23:56-62.Crossref 19. Asberg M, Cronholm B, Sjoqvist F, Tuck D: Correlation of subjective side effects with plasma concentrations of nortriptyline . Br Med J 1970;4:18-21.Crossref 20. Amsterdam JD, Brunswick D, Potter L, Kaplan MJ: Cimetidineinduced alterations in desipramine plasma levels . Psychopharmacology 1984;83:373-375.Crossref 21. Suckow RF, Cooper TB: Simultaneous determination of imipramine, desipramine, and their 2-hydroxy metabolites in plasma by ion-pair reversed-phase high-performance liquid chromatography with amperometric detection . J Pharm Sci 1981;70:257-261.Crossref 22. ZarJH: Biostatistical Analysis . Englewood Cliffs, NJ, Prentice-Hall Inc, 1974. 23. Gram LF: Metabolism of tricyclic antidepressants: A review . Dan Med Bull 11974;21:218-231. 24. Potter WZ, Calil HM, Sutfin TA, Zavadil AP, Jusko WJ, Rapoport J, Goodwin FK: Active metabolites of imipramine and desipramine in man . Clin Pharmacol Ther 1982;32:393-401.Crossref 25. Narasimhachari N, Saady JJ, Joseph A, Ettigi P, Friedel RO: Evidence for in vivo methylation of the secondary amine antidepressant desipramine to imipramine . J Clin Psychopharmacol 1982;6:413-416. 26. Brunswick DJ, Mendels J: Reduced levels of tricyclic antidepressants in plasma from Vacutainers . Community Psychopharmacol 1977;1:131-134.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Apr 1, 1985

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